• Korean Journal of Clinical Laboratory Science
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• v.53 no.4
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• pp.333-341
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• 2021

Benzodiazepines (BDZs) drugs act on the GABA_A receptor, function as nerve suppressors, and are used to treat anxiety, insomnia, and panic disorder. We analyzed the data of 30 individuals to determine any differences in the sleep-electroencephalogram findings among individuals varying in age, benzodiazepine use, and duration of benzodiazepine use. Comparisons between users and non-users of benzodiazepines, short-term and long-term users, older and younger users, and older short-term and older long-term users, were achieved using electroencephalographic findings obtained through polysomnography. The parameters evaluated included sleep latency, sleep efficiency, sleep-stage percentages, number of sleep spindles, and average frequency of sleep-spindle. The difference between benzodiazepine users and non-users was significant with respect to sleep-stage percentages and average frequency of sleep-spindle. Older and younger users differed significantly with respect to sleep efficiency and sleep-stage percentages, whereas significant difference for sleep efficiency was obtained between long-term and short-term users. Taken together, our results indicate that BDZ consumption suppresses slow-wave sleep and increases the frequency of sleep spindles.

• 대한핵의학회:학술대회논문집
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• 2003.11a
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• pp.28.1-28.1
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• 2003

• Anxiety and mood
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• v.11 no.2
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• pp.143-148
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• 2015

Objective : This study examined benzodiazepine prescription patterns of outpatients visiting the psychiatry department in a single general hospital in Korea. Methods : A retrospective descriptive analysis of benzodiazepine prescriptions was performed on a database from 2014 in a general hospital in Korea. We analyzed the following factors of adult outpatients: demographic factors such as sex and age, amount of benzodiazepine prescribed, treatment duration, and diagnosis based on the ICD-10. Results : In 2014, benzodiazepines were prescribed to 46.4% of the outpatients. Percentage of benzodiazepine prescription increased with age and was highest in the age group 40-59 years. Prescription was more prevalent in women and the prescription percentage increased by treatment duration. Patients with the F4 diagnosis (neurotic, stress-related and somatoform disorders) were the most highly prescribed group. For all diagnosis groups, prescription was more prevalent in females or similar for both sexes except for patients with F5 diagnosis (behavioral syndromes associated with physiological disturbances and physical factors), with males being more predominant. Conclusion : Despite the concern regarding the rate of benzodiazepine prescription and administration to geriatric patients, long-term prescription and usage among older patients is still prevalent.

• Korean Journal of Psychosomatic Medicine
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• v.30 no.2
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• pp.112-118
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• 2022

Objectives : Zolpidem is a common drug used in insomnia. However, there are several reports of side effects of the central nervous system or sleep related behavior in patients who took zolpidem. This study was conducted to investigate risk factors affecting sleep related behavior after taking zolpidem in inpatients. Methods : From January 1, 2019 to December 31, 2019, medical records of patients who took zolpidem hospitalized at Inha University Hospital were reviewed retrospectively. Results : 907 patients who took Zolpidem, 102 (11.2%) showed sleep related behavior, and if they were 65 years of age or older, men, taking antipsychotics, and taking antipsychotics and benzodiazepines at the same time, they were significantly more likely to show sleep related behavior. Conclusions : Risk factors for sleep-related behavior after use of zolpidem are estimated gender, elderly, antipsychotics, and combination of antipsychotics and benzodiazepines.

• The Korean Journal of Nuclear Medicine
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• v.33 no.6
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• pp.527-536
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• 1999

Purpose: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F-18]fluoro)flumazenil, a new fluorine-18 ($t_{1/2}$= 110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. Materials and Methods: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at $85^{\circ}C$ in the hot ceil for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. Results: The total chemical yield of tosylated flumazenil derivative was ${\sim}40%$. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were $2.5{\pm}0.37,\;2.2{\pm}0.26,\;2.1{\pm}0.11$ and blood activities were $3.7{\pm}0.43,\;3.3{\pm}0.07,\;3.3{\pm}0.09%ID/g$, respectively. Conclusion: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.

• Journal of The Korean Society of Clinical Toxicology
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• v.14 no.1
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• pp.26-32
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• 2016

Purpose: Aspiration pneumonia is an important complication of drug intoxication with decreased mental status. The purpose of the study is to investigate the risk factors of aspiration pneumonia in the patients of benzodiazepine overdose with or without co-ingestion of other drugs. Methods: A retrospective chart review of patients who visited the emergency department between January 2012 and December 2014 was conducted. Demographic data, time from ingestion to visit, initial vital signs, symptoms, mental status, medical history, laboratory results, chest radiological findings and co-ingested medications were recorded. Multiple logistic analyses were performed to verify the association between variables and the development of aspiration pneumonia. Results: A total of 249 patients presented to the emergency department with benzodiazepine overdose. Aspiration pneumonia had developed in 24 patients (9.6%). Univariate analysis revealed time from ingestion to visit was longer, Glasgow coma scale score was lower, hypoxia was presented, leukocytosis was shown, types of ingested drugs was high, less activated charcoal was applied and tricyclic antidepressants was taken in patients that developed aspiration pneumonia. Time from ingestion to visit (odds ratio (OR) 1.121, 95% confidence interval (CI), 1.057-1.189, p=0.000), GCS score (OR 0.724. 95% CI, 0.624-0.839, p=0.000), oxygen saturation (OR 0.895, 95% CI, 0.835-0.959, p=0.002), and co-ingestion of TCA (OR 4.595, 95% CI, 1.169-18.063, p=0.029) were identified as risk factors of morbidity of aspiration pneumonia upon multiple logistic regression analysis. Conclusion: Time from ingestion to visit, low GCS score, low oxygen saturation and co-ingestion of TCA were risk factors of the development of aspiration pneumonia in benzodiazepine overdose patients.

• Sleep Medicine and Psychophysiology
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• v.12 no.2
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• pp.144-147
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• 2005

Objective: The authors would like to find the relationship between zolpidem and nocturnal eating episodes in diverse psychiatric patients. Method: We evaluated case series of 6 patients who showed nocturnal eating episodes after takine zolpidem. Results: We have experienced 6 cases who showed nocturnal eating behavior after taking zolpidem. They included 3 patients with schizoprenia, a patient with major depressive disorder, a patient with PTSD and a patient with bipolra I disorder. With reducing or discontiuation of zolpidem, their nocturanl eating resolved. Conclusion: This finding strongly suggests the relationship between zolpidem and the nocturnal eating episode. Physicians should be aware that zolpidem might induce nocturnal eating behaviors.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.4
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• pp.337-343
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• 2009

Purpose: ((R)-1-(2-chlorophenyl)-N-1-[$^{11}$C]methyl-N(1-propyl)-3-isoquinoline carboxamide ((R)-PK11195) is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a direct and simple radiosynthesis of [$^{11}$C](R)-PK11195 in mild condition using NaH suspension in DMF and one-step loop method. Materials and Methods: (R)-N-Desmethyl-PK11195 (1 mg) in DMSO (0.1 mL) and NaH suspension in DMF (0.1 mL) were injected into a semi-prep HPLC loop. [$^{11}$C]methyl iodide was passed through HPLC loop at room temperature. Purification was performed using semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. Results: The labeling efficiency of [$^{11}$C](R)-PK11195 was 71.8$\pm$8.5%. The specific activity was 11.8:$\pm$6.4 GBq/$\mu$mol and radiochemical purity was higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. Conclusion: By the one-step loop method with the [$^{11}$C]CH3l automated synthesis module, [$^{11}C$](R)-PK11195 could be easily prepared in high radiochemical yield using NaH suspension in DMF.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.2
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• pp.116-125
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• 2020

Objectives : Self-poisoning is the leading cause of visits to the emergency departments after a suicide attempts. This study is aimed to compare the patient characteristics according to the category of drugs ingested by the patients who attempted suicide. Methods : All medical charts were retrospectively reviewed from patients who visited the emergency center, at Seoul Medical Center, due to intentional self-poisoning from April of 2011 to July of 2019. We investigated the information regarding the subtype and quantity of the intoxication drug, how it was obtained, suicidal history, and psychiatric history, as well as, sociodemographic information. Variables were compared between prescription drug (PD) and non-prescription drug (NPD) poisoning groups. Results : The mean age of the NPD poisoning group was significantly lower than that of the PD poisoning group. The patient ratio of those enrolled in national health insurance and living with spouses were significantly higher in the NPD poisoning group. Compared to the NPD poisoning group, the PD poisoning group had a higher incidence of mental illnesses, underlying diseases and ratio of involuntary visit to the emergency department. Among the prescription drugs, the benzodiazepine poisoning group had a higher rate of self-prescription than the non-poisoning group, while the zolpidem poisoning group had a higher rate of the using someone else's prescription than other drugs. Each single drug poisoning group (benzodiazepine, zolpidem, and antidepressant single-agent) had a higher rate of no mental illness than each of the mixed-poisoning group. Conclusions : Guidelines for regulating non-prescription drugs are needed as a matter of suicide prevention. Also, this study suggests that clinicians need to be careful when issuing prescriptions and should suicidal risk according to patients' characteristics, duration of follow-up and type of drug packaging.

• Sleep Medicine and Psychophysiology
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• v.26 no.2
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• pp.86-103
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• 2019

Objectives: The objective of this study was to develop evidence- and consensus-based clinical safety usage guidelines for sedative hypnotics using the Delphi technique. Methods: A group of 15 sleep experts from Korean Academy of Sleep Medicine were chosen for this study comprising a three-round web-based Delphi survey. The first round survey was composed of 39 questions to identify problems with sedative hypnotics usage in Korean clinical practice and the result roughly outlined what should be included in the guidelines. The second round survey was composed of 21 questions to collect specific opinions of experts on clinically important issues in prescribing sedative hypnotics, and its result provided the basis for the guidelines. A third round survey aimed to evaluate the reliability and validity of the established guidelines. Results: In the third round, all 17 items showed a median of 4 or more, with an average of 4.12 and a standard deviation of 0.32. Thus we present safety usage guidelines with 13 propositions for prescription, maintenance, and withdrawal of sedative hypnotics. Conclusion: The safety usage guidelines on sedative hypnotics developed from this study could lead to safe and effective prescription of hypnotics in clinical practice, especially for the non-experts in sleep medicine. Furthermore, the guidelines will help to improve the quality of insomnia treatment by contributing to the establishment of a safe regime for sedative hypnotics without excessive use of drugs.